Acesulfame Potassium Compositions and Processes for Producing Same

ABSTRACT

Improved processes for producing high purity acesulfame potassium. In one embodiment, the process comprises the steps of contacting a solvent, e.g., dichloromethane, and a cyclizing agent, e.g., sulfur trioxide, to form a cyclizing agent composition and reacting an acetoacetamide salt with the cyclizing agent in the composition to form a cyclic sulfur trioxide adduct. The contact time is less than 60 minutes. The process also comprises forming from the cyclic sulfur trioxide adduct composition a finished acesulfame potassium composition comprising non-chlorinated, e.g., non-chlorinated, acesulfame potassium and less than 35 wppm 5-halo acesulfame potassium, preferably less than 5 wppm.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/397,540, filed Sep. 21, 2016, the disclosure of which isincorporated herein by reference in its entirety.

FIELD OF INVENTION

The present invention relates generally to acesulfame potassium and toprocesses for producing acesulfame potassium. More specifically, thepresent invention relates to processes for producing high purityacesulfame potassium.

BACKGROUND OF THE INVENTION

Acesulfame potassium has an intense, sweet taste and has been used inmany food-related applications as a sweetener. In conventionalacesulfame potassium production processes, sulfamic acid and an amine,e.g., triethylamine, are reacted to form an amidosulfamic acid salt,such as a trialkyl ammonium amidosulfamic acid salt. The amidosulfamicacid salt is then reacted with diketene to form an acetoacetamide salt.The acetoacetamide salt may be cyclized, hydrolyzed, and neutralized toform acesulfame potassium. U.S. Pat. Nos. 5,744,010 and 9,024,016disclose exemplary acesulfame potassium production processes.

Typically, the acetoacetamide salt intermediate is cyclized by reactionwith sulfur trioxide in an inorganic or organic solvent to form a cyclicsulfur trioxide adduct. The solvent routinely utilized in this reactionis an organic solvent such as a halogenated, aliphatic hydrocarbonsolvent, for example, dichloromethane. The adduct formed by thisreaction is subsequently hydrolyzed and then neutralized with potassiumhydroxide to form acesulfame potassium.

Acesulfame potassium and the intermediate compositions produced byconventional methods contain undesirable impurities, such as5-chloro-acesulfame potassium. Limits for the content of variousimpurities are often set by governmental regulations or customerguidelines. Due to their similar chemical structures and properties,separation of 5-chloro-acesulfame potassium from the desirednon-chlorinated acesulfame potassium, using standard purificationprocedures such as crystallization has proven difficult, resulting inconsumer dissatisfaction and the failure to meet regulatory standards.

The need exists for an improved process for producing high purityacesulfame potassium compositions in which the formation of5-chloro-acesulfame potassium during synthesis is reduced or eliminated.

All of the references discussed herein are hereby incorporated byreference.

SUMMARY OF THE INVENTION

The application discloses processes for producing a finished acesulfamepotassium composition, the process comprising the steps of: contacting asolvent and a cyclizing agent to form a cyclizing agent composition,reacting an acetoacetamide salt with the cyclizing agent in thecyclizing agent composition to form a cyclic sulfur trioxide adduct, andforming from the cyclic sulfur trioxide adduct the finished acesulfamepotassium composition comprising non-chlorinated acesulfame potassiumand less than 35 wppm 5-chloro-acesulfame potassium, e.g., from 0.001wppm to 2.7 wppm 5-chloro-acesulfame potassium. Contact time from thebeginning of contacting step to the beginning of the reacting step isless than 60 minutes. The forming of the finished acesulfame potassiumcomposition may comprise: hydrolyzing the cyclic sulfur trioxide adductto form an acesulfame-H composition comprising acesulfame-H,neutralizing the acesulfame-H in the acesulfame-H composition to form acrude acesulfame potassium composition comprising non-chlorinatedacesulfame potassium and less than 35 wppm 5-chloro-acesulfamepotassium, and forming the finished acesulfame potassium compositionfrom the crude acesulfame potassium composition. The finished acesulfamepotassium composition may comprise from 0.001 wppm to 5 wppm5-chloro-acesulfame potassium. In some cases, the contact time is lessthan 15 minutes and the crude acesulfame potassium composition comprisesfrom 0.001 wppm to 5 wppm 5-chloro-acesulfame potassium and the finishedacesulfame potassium composition comprises from 0.001 wppm to 5 wppm5-chloro-acesulfame potassium. In one embodiment, the contact time isless than 5 minutes and the crude acesulfame potassium compositioncomprises from 0.001 wppm to 5 wppm 5-chloro-acesulfame potassium andthe finished acesulfame potassium composition comprises from 0.001 wppmto 2.7 wppm 5-chloro-acesulfame potassium. The finished acesulfamepotassium composition may comprise at least 90% by weight of the5-chloro-acesulfame potassium present in the crude acesulfame potassiumcomposition. In some case, the hydrolyzing comprises adding water to thecyclic sulfur trioxide adduct to form a hydrolysis reaction mixture, andwherein the temperature of the hydrolysis reaction mixture is maintainedat a temperature ranging from −35° C. to 0° C. The finished acesulfamepotassium composition may comprise from 0.001 wppm to 5 wppm organicimpurities and/or from 0.001 wppm to 5 wppm heavy metals. Preferably,the process further comprises the steps of reacting sulfamic acid and anamine to form an amidosulfamic acid salt, and reacting the amidosulfamicacid salt and acetoacetylating agent to form the acetoacetamide salt.The cyclizing agent composition may comprise less than 1 wt % ofcompounds selected from chloromethyl chlorosulfate,methyl-bis-chlorosulfate, and mixtures thereof. The reacting isconducted for a cyclization reaction time, from the start of thereactant feed to the end of the reactant feed, less than 35 minutes. Theweight ratio of solvent to cyclizing agent in the cyclizing agentcomposition may be at least 1:1. The processes may further comprisecooling the cyclizing agent composition to a temperature less than 15°C. Preferably, the cyclizing agent comprises sulfur trioxide and thesolvent comprises dichloromethane. In one embodiment, the processescomprise the steps of: reacting sulfamic acid and triethylamine to forman amidosulfamic acid salt, reacting the amidosulfamic acid salt anddiketene to form the acetoacetamide salt, contacting dichloromethane anda sulfur trioxide to form a cyclizing agent composition (optionallycooling the cyclizing agent composition to a temperature less than 15°C.), reacting the acetoacetamide salt with the sulfur trioxide in thecyclizing agent composition to form a cyclic sulfur trioxide adduct,hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-Hcomposition, and neutralizing the acesulfame-H to form the finishedacesulfame potassium composition comprising non-chlorinated acesulfamepotassium and less than 10 wppm 5-chloro-acesulfame potassium, andcontact time from the beginning of step (a) to the beginning of step (b)may be less than 10 minutes. The application also describes crude,intermediate, and finished acesulfame potassium composition produced bythe processes described herein, e.g., a finished acesulfame potassiumcomposition comprising non-chlorinated acesulfame potassium, from 0.001wppm to 2.7 wppm 5-chloro acesulfame potassium, and from 0.001 wppm to 5wppm heavy metals.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described in detail below with reference to theappended drawing.

FIG. 1 is a process flow sheet of an acesulfame potassium productionprocess in accordance with one embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION Introduction

Conventional processes for producing acesulfame potassium involvereacting sulfamic acid and an amine in the presence of acetic acid toform an amidosulfamic acid salt. The amidosulfamic acid salt is thenreacted with an acetoacetylating agent, e.g., diketene, to form anacetoacetamide salt. The acetoacetamide salt is reacted with a cyclizingagent, e.g., sulfur trioxide, to form a cyclic sulfur trioxide adduct.The cyclic sulfur trioxide adduct is then hydrolyzed and neutralized viaconventional means to form a crude acesulfame potassium compositioncomprising acesulfame potassium. This composition is phase separatedinto aqueous and organic phases. Most of the acesulfame potassiumseparates into the aqueous phase. As used herein, the term “crudeacesulfame potassium composition” refers to the initial product of theneutralization reaction or to the aqueous phase that is formed from thephase separation step (without any further purification). The crudeacesulfame potassium composition comprises at least 5 wt % acesulfamepotassium. The crude acesulfame potassium composition may be optionallytreated to form an “intermediate acesulfame potassium composition”and/or a “finished acesulfame potassium composition,” which arediscussed below.

Conventional acesulfame potassium compositions have been shown tocomprise several undesirable impurities, among them 5-chloro-acesulfamepotassium and acetoacetamide. Content limits for these compounds in thefinished acesulfame potassium composition are often determined byindustry purity standards and/or by standards established for particularend use products that utilize acesulfame potassium as a sweetener. Insome cases, limits for these impurities are determined by governmentalregulations. For most applications, high acesulfame potassium puritylevels are preferred. Because the chemical structure of5-chloro-acesulfame potassium is similar to that of non-chlorinatedacesulfame potassium, separation of 5-chloro-acesulfame potassium usingstandard purification procedures such as crystallization has provendifficult.

Without being bound by theory, it has now been discovered that thereaction of the cyclizing agent with the acetoacetamide salt to form thecyclic sulfur trioxide adduct may also involve side reactions that formthe 5-chloro-acesulfame potassium impurity.

The use of specific reaction parameters, however, may advantageouslyreduce or eliminate 5-chloro-acesulfame potassium formation or theformation of its precursor, 5-chloro-acesulfame-H. In particular, it hasnow been discovered that limiting contact time, as discussed below,surprisingly reduces or eliminates 5-chloro-acesulfame potassiumformation in the crude, intermediate, and/or finished acesulfamepotassium compositions. In addition, the reduced impurity levels inthese acesulfame potassium compositions reduce or eliminate the need foradditional purification steps, resulting in overall improved processefficiency.

It is postulated that the contacting of the cyclizing agent, thesolvent, and optionally other components may lead to the formation ofchlorine/chloride-containing compounds. Exemplary cyclizingagent/solvent reaction products include halogen-containing compoundssuch as chlorine/chloride-containing compounds, e.g., chlorosulfates.These compounds, in turn, may react to chlorinate the acesulfameprecursor acid, acesulfame-H, sometimes referred to as sweetener acid,or its precursors, e.g., acetoacetamide-N-sulfonate. By limiting thecontact time, lower amounts of chlorine/chloride-containing compoundsare formed, e.g., chlorosulfates, are formed (as compared to the amountformed when longer contact times are employed). That is, shorter contacttimes have now been shown to retard the formation ofchlorine/chloride-containing compounds, e.g., chlorosulfates. As aresult of the shorter contact times, in one embodiment, the cyclizingagent composition may have a low chlorine/chloride-containing compoundcontent, e.g., a low chlorosulfate content, as discussed herein. Thereduction or elimination of chlorine/chloride-containing compoundsdirectly leads to the formation of higher purity crude acesulfamepotassium compositions discussed herein, thereby simplifying subsequenttreatment operations for forming the intermediate or finished acesulfamepotassium compositions. The process also advantageously leads to theformation of intermediate and finished acesulfame potassium compositionshaving low 5-chloro-acesulfame potassium content.

Additional specific terms that are used herein are now defined. “Contacttime,” as used herein, refers to the time period that the solventcontacts the cyclizing agent before formation of the cyclic sulfurtrioxide adduct. Thus, contact time begins when at least some of thesolvent contacts at least some the cyclizing agent to form the cyclizingagent/solvent mixture (“cyclizing agent composition”), and contact timeends when the acetoacetamide salt first contacts the cyclizing agent inthe cyclizing agent composition.

“Residence time,” as used herein, refers to the time period that acomposition (or stream) to be treated, e.g., a crude acesulfamepotassium composition, remains in a particular treatment operation.Residence time begins when the composition to be treated enters thetreatment operation, and residence time ends when the resultantcompositions (formed via the treatment) exit the treatment operation. Asone particular example, residence time for a concentrating operation,e.g., evaporation, refers to the time from when a crude acesulfamepotassium composition enters the evaporator until the intermediateacesulfame potassium composition exits the evaporator. As anotherexample, residence time for a separating operation, e.g.,crystallization, refers to the time from when a crude acesulfamepotassium composition enters the crystallizer until the intermediateacesulfame potassium composition exits the crystallizer.

“Cyclization reaction time,” as used herein, refers to the time from thestart of the acetoacetamide salt feed to the termination of theacetoacetamide salt feed. In some cases, if indicated, the cyclizationreaction time may include additional time past the termination of theacetoacetamide salt feed, e.g., an extra 5 minutes or an extra minute.

“5-chloro-acesulfame potassium,” as used herein, refers to the followingmolecule:

“Acetoacetamide,” as used herein, refers to the following molecule:

“Acetoacetamide-N-sulfonic acid” as used herein, refers to the moleculeshown below. In some cases, acetoacetamide-N-sulfonic acid may be adegradation product of acesulfame potassium or acesulfame-H. The term“acetoacetamide-N-sulfonic acid,” as used herein, also includes salts ofacetoacetamide-N-sulfamic acid, e.g., potassium, sodium, and otheralkali metal salts.

An “intermediate acesulfame potassium composition” refers to acomposition resulting from the concentrating of the crude acesulfamepotassium composition, e.g., the removal of water from the crudeacesulfame potassium composition. The intermediate acesulfame potassiumcomposition comprises at least 10 wt % acesulfame potassium, based onthe total weight of the intermediate acesulfame potassium composition,and has an acesulfame potassium weight percentage that is higher thanthat of the crude acesulfame potassium composition.

A “finished acesulfame potassium composition” refers to a composition(preferably directly) resulting from the separating, e.g., crystallizingand/or filtering, of the intermediate acesulfame potassium composition,e.g. no further process steps are preferably conducted after theseparating of the intermediate acesulfame potassium composition in orderto obtain the finished acesulfame potassium composition. The finishedacesulfame potassium composition comprises at least 15 wt % acesulfamepotassium, based on the total weight percentage of the finishedacesulfame potassium composition, and has an acesulfame potassium weightpercentage that is higher than that of the intermediate acesulfamepotassium composition.

“Wppm” and “wppb,” as used herein, mean weight parts per million orweight parts per billion, respectively. These are based on the totalweight of the respective composition, e.g., the total weight of theentire crude acesulfame potassium composition or the entire finishedacesulfame potassium composition.

Acesulfame Potassium Formation (Contact Time)

Processes for producing acesulfame potassium exhibiting high puritylevels are described herein. In one embodiment, the process comprisesthe steps of contacting a solvent and a cyclizing agent to form acyclizing agent composition and reacting an acetoacetamide salt with thecyclizing agent (in the cyclizing agent composition) to form a cyclicsulfur trioxide adduct. Importantly, the contact time is less than 60minutes. The process also comprises forming a finished acesulfamepotassium composition from the cyclic sulfur trioxide adductcomposition.

The contacting of the solvent and the cyclizing agent is contemplatedbroadly. In some embodiments, the contacting methods include theaddition of solvent to cyclizing agent, the addition of cyclizing agentto solvent. The components may be fed, e.g., simultaneously fed to avessel. Addition/mixing and/or co-feeding (optionally simultaneous) ofthese components are contemplated.

The reaction of the acetoacetamide salt and the cyclizing agent may beconducted by contacting the two reactants. The reactants may be fed,e.g., simultaneously fed to a vessel. In one embodiment, theacetoacetamide salt may be added to the cyclizing agent in the cyclizingagent composition. The cyclizing agent in the cyclizing agentcomposition may be added to the acetoacetamide salt. Addition/mixingand/or co-feeding (optionally simultaneous) of the reactants are alsocontemplated. In one embodiment, the cyclizing agent composition may becontained in a vessel and the acetoacetamide salt may be added to thecyclizing agent composition, e.g., added drop-wise to the cyclizingagent composition.

In some embodiments, contact time is less than 60 minutes, e.g., lessthan 45 minutes, less than 30 minutes, less than 15 minutes, less than10 minutes, less than 8 minutes, less than 5 minutes, less than 3minutes, or less than 1 minute. In one embodiment, the solvent andcyclizing agent are mixed and immediately reacted with theacetoacetamide salt. In terms of ranges, contact time may range from 1second to 60 minutes, e.g., from 1 second to 45 minutes, from 1 secondto 30 minutes, from 1 second to 15 minutes, from 1 second to 10 minutes,from 1 minute to 45 minutes, from 1 minute to 30 minutes, from 1 minuteto 15 minutes, from 1 minute to 10 minutes, from 10 seconds to 45minutes, from 10 seconds to 30 minutes, from 30 seconds to 30 minutes,from 1 minute to 10 minutes, from 3 minutes to 10 minutes, or from 5minutes to 10 minutes. Contact time may be at least 1 second, e.g., atleast 5 seconds, at least 30 seconds, at least 1 minute, at least 5minutes, at least 10 minutes, at least 15 minutes, or at least 30minutes.

By limiting the contact time as discussed herein, fewer cyclizingagent/solvent reaction products, e.g., chlorosulfates, are formed. Thecyclizing agent composition, for example, may have a low cyclizingagent/solvent reaction product content, e.g., a low chlorosulfatecontent. For example, the cyclizing agent composition may comprise lessthan 1 wt % cyclizing agent/solvent reaction product, e.g., less than0.75 wt %, less than 0.5 wt %, less than 0.25 wt %, less than 0.1 wt %,less than 0.05 wt %, or less than 0.01 wt %. In terms of ranges, thecyclizing agent composition may comprise from 1 ppm to 1 wt % cyclizingagent/solvent reaction products, e.g., from 10 ppm to 1 wt %, from 10ppm to 0.75 wt %, from 10 ppm to 0.5 wt %, from 10 ppm to 0.25 wt %,from 100 ppm to 0.75 wt %, from 100 ppm to 0.5 wt %, or from 100 ppm to0.25 wt %. These ranges and limits apply to cyclizing agent/solventreaction products generally and to specific reaction products generally,e.g., chloromethyl chlorosulfate, methyl-bis-chlorosulfate, andcombinations thereof.

Exemplary chlorosulfates include chloromethyl chlorosulfate andmethyl-bis-chlorosulfate. These reaction products may be formed when achlorine-containing solvent is employed. In one embodiment, thecyclizing agent composition comprises less than 1 wt % chloromethylchlorosulfate and/or methyl-bis-chlorosulfate, e.g., less than 0.75 wt%, less than 0.5 wt %, less than 0.25 wt %, less than 0.1 wt %, lessthan 0.05 wt %, or less than 0.01 wt %. In one embodiment, the cyclizingagent composition comprises less than 1 wt % chloromethyl chlorosulfate,e.g., less than 0.75 wt %, less than 0.5 wt %, less than 0.25 wt %, lessthan 0.1 wt %, less than 0.05 wt %, or less than 0.01 wt %. In oneembodiment, the cyclizing agent composition comprises less than 1 wt %methyl-bis-chlorosulfate, e.g., less than 0.75 wt %, less than 0.5 wt %,less than 0.25 wt %, less than 0.1 wt %, less than 0.05 wt %, or lessthan 0.01 wt %.

In one embodiment, the solvent and cyclizing agent are combined in afirst vessel, e.g., a first reactor, to form a cyclizing agentcomposition, which optionally may be cooled. The cyclizing agentcomposition may then be added to the acetoacetamide salt in a secondreactor. In one embodiment, the first vessel is chilled, e.g., totemperature below 35° C., prior to combining the solvent and cyclizingagent. In some cases, the cyclizing agent and the solvent are cooledindividually and then fed to the reaction with the acetoacetamide salt,optionally followed by additional cooling. In one embodiment, the firstvessel itself is chilled, e.g., to a temperature below 15° C., prior tocontacting the solvent and cyclizing agent, which leads to the coolingof the solvent and the cyclization that may be added to the firstvessel. In some cases, the cyclizing agent and the solvent are cooledindividually and then combined and fed to the reaction with theacetoacetamide salt.

In some cases, the process comprises the steps of providing a cyclicsulfur trioxide adduct composition comprising less than 1 wt % cyclizingagent/solvent reaction products, e.g., chloromethyl chiorosulfate and/ormethyl-bis-chlorosulfate, and forming the acesulfame potassiumcomposition from the cyclic sulfur trioxide adduct composition. Theproviding of the cyclic sulfur trioxide adduct composition may varywidely as long as the cyclic sulfur trioxide adduct composition has therequired cyclizing agent/solvent reaction product content. The cyclicsulfur trioxide adduct composition optionally is formed using any of themethods described herein.

In some embodiments, the cyclizing agent composition is provided at alow temperature and/or is cooled to yield a cooled cyclizing agentcomposition having a low temperature. The cooling or the providing ofthe low temperature cyclizing agent composition may be achieved throughany of a variety of different cooling techniques. For example, thecooling step may be achieved by using one or more heat exchangers,refrigeration units, air cooling units, water cooling units, or acooling medium, such as liquid nitrogen or other cryogenics. If heatexchangers are employed, a water/glycol mixture is a preferable exchangemedium, with brine being a suitable alternative.

In some embodiments, the cyclizing agent composition is provided at oris cooled to a temperature less than 15° C., e.g., less than 12° C.,less than 11° C., less than 10° C., less than 8° C., less than 5° C.,less than 3° C., less than 1° C., or less than 0° C. In terms of ranges,the cyclization agent composition is cooled to a temperature rangingfrom −20° C. to 15° C., e.g., from −15° C. to 15° C., from −10° C. to12° C., from −8° C. to 10° C., or −8° C. to 5° C. In some embodiments,the cooling step reduces the temperature of the cyclizing agentcomposition (as provided), e.g., by at least 2° C., at least 3° C., atleast 5° C., at least 10° C., at least 15° C., at least 20° C., or atleast 25° C.

In one embodiment, only the cyclizing agent (e.g., without solvent) iscooled, and then the cooled cyclizing agent is mixed with the solvent toform the cyclizing agent composition, which is then reacted with theacetoacetamide salt. That is, in some cases, the solvent (if present)may not be cooled in the same manner as the cyclizing agent is cooled.In other embodiments, the solvent is cooled prior to being mixed withthe cyclizing agent to form the cyclizing agent composition, optionallyfollowed by additional cooling of the resulting cyclizing agentcomposition.

In some cases, the cooling is implemented via multiple cooling steps.For example, the solvent may be cooled to a first temperature, thencombined with the cyclizing agent to form the cyclizing agentcomposition, which is then further cooled to a second temperature, whichis less than the first temperature. In some embodiments, the cyclizingagent is cooled to a first temperature, the solvent is cooled to asecond temperature, and the cooled cyclizing agent and the cooledsolvent are combined and optionally cooled to a third temperature, whichis less than the first and second temperatures. These cooling schemesare merely exemplary and are not intended to limit the scope of thecooling step.

It has also been discovered that if cyclization reaction time isminimized, the formation of impurities, e.g., organic impurities, suchas 5-chloro-acesulfame potassium, is reduced or eliminated. In someembodiments, the cyclization reaction is conducted for a cyclizationreaction time, less than 35 minutes, e.g., less than 30 minutes, lessthan 25 minutes, less than 20 minutes, less than 15 minutes, or lessthan 10 minutes. In terms of ranges, the cyclization reaction may beconducted for a cyclization reaction time ranging from 1 second to 35minutes, e.g., from 10 seconds to 25 minutes, from 30 seconds to 15minutes, or from 1 minute to 10 minutes.

The cyclic sulfur trioxide adduct may be subjected to one or more stepsto form the finished acesulfame potassium composition. In some cases,the formation of the finished acesulfame potassium composition comprisesthe steps of hydrolyzing (at least some of) the cyclic sulfur trioxideadduct to form an acesulfame-H composition comprising acesulfame-H andneutralizing the acesulfame-H in the acesulfame-H composition to form acrude acesulfame potassium composition.

Crude acesulfame compositions may be treated to form intermediateacesulfame potassium compositions and (subsequently) finished acesulfamecompositions, and this treatment operation may include one or moreconcentrating or separating operations.

For example, the treatment operation may comprise concentrating thecrude acesulfame potassium composition to form a water stream and anintermediate acesulfame potassium composition and then separating theintermediate acesulfame potassium composition to form the finishedacesulfame potassium composition comprising acesulfame potassium, e.g.,via filtration and/or crystallization.

Acesulfame Potassium Compositions

The crude acesulfame potassium composition is formed by hydrolyzing thecyclic sulfur trioxide adduct to form an acesulfame-H composition andneutralizing the acesulfame-H in the acesulfame-H composition to formthe crude acesulfame potassium composition, as discussed herein. Theproduct of the neutralization step is phase separated into aqueous andorganic phases. The crude acesulfame potassium composition may beobtained from the aqueous phase (without any further purification). Thecrude acesulfame potassium composition preferably comprises a mixture ofacesulfame potassium, e.g., non-chlorinated acesulfame potassium, andless than 35 wppm 5-chloro-acesulfame potassium, e.g., less than 30wppm, less than 25 wppm, less than 20 wppm, less than 15 wppm, less than12 wppm, less than 10 wppm, less than 7 wppm, less than 5 wppm, lessthan 3 wppm, or less than 1 wppm. In some cases the crude acesulfamepotassium composition is free of 5-chloro-acesulfame potassium, e.g.,substantially free of 5-chloro-acesulfame potassium (undetectable). Interms of ranges, the crude acesulfame potassium composition may comprisefrom 1 wppb to 35 wppm 5-chloro-acesulfame potassium, e.g., from 1 wppbto 20 wppm, from 1 wppb to 10 wppm, from 1 wppb to 5 wppm, from 1 wppbto 2.7 wppm, from 10 wppb to 20 wppm, from 10 wppb to 19 wppm, from 10wppb to 15 wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from10 wppb to 5 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm,or from 100 wppb to 5 wppm.

The finished acesulfame potassium compositions, which are typicallysuitable for end consumer usage, are formed by treating the crudeacesulfame potassium composition to remove impurities, as discussedherein. This finished acesulfame potassium composition preferablycomprises a mixture of acesulfame potassium, e.g., non-chlorinatedacesulfame potassium, and less than 35 wppm 5-chloro-acesulfamepotassium, e.g., less than 30 wppm, less than 25 wppm, less than 20wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than7 wppm, less than 5 wppm, less than 3 wppm, or less than 1 wppm. In somecases the finished acesulfame potassium composition is free of5-chloro-acesulfame potassium, e.g., substantially free of5-chloro-acesulfame potassium (undetectable). In terms of ranges, thefinished acesulfame potassium composition may comprise from 1 wppb to 35wppm 5-chloro-acesulfame potassium, e.g., from 1 wppb to 20 wppm, from 1wppb to 10 wppm, from 1 wppb to 5 wppm, from 1 wppb to 2.7 wppm, from 10wppb to 20 wppm, from 10 wppb to 19 wppm, from 10 wppb to 15 wppm, from10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppb to 5 wppm,from 100 wppb to 15 wppm, from 100 wppb to 10 wppm, or from 100 wppb to5 wppm. The shorter contact times reduce or eliminate5-chloro-acesulfame potassium formation, resulting in both a crudeacesulfame potassium composition and a finished acesulfame potassiumcomposition having low 5-chloro-acesulfame potassium content.

In some embodiments, the finished acesulfame potassium compositionscomprise acesulfame potassium and less than 33 wppm acetoacetamide,e.g., less than 32 wppm, less than 30 wppm, less than 25 wppm, less than20 wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, lessthan 7 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, lessthan 0.8 wppm, less than 0.5 wppm, or less than 0.3 wppm. In some casesthe finished acesulfame potassium composition is free of acetoacetamide,e.g., substantially free of acetoacetamide (undetectable). In terms ofranges, the finished acesulfame potassium composition may comprise from1 wppb to 33 wppm acetoacetamide, e.g., from 10 wppb to 32 wppm, from 10wppb to 25 wppm, from 10 wppb to 15 wppm, from 10 wppb to 12 wppm, from10 wppb to 10 wppm, from 10 wppb to 7 wppm, from 10 wppb to 5 wppm, from10 wppb to 3 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm,or from 100 wppb to 5 wppm. In some cases, acetoacetamide-N-sulfonicacid may also be present in the finished acesulfame potassiumcompositions in the aforementioned amounts. These impurities may beformed by side reactions and degradation of the acesulfame potassium andacesulfame-H molecules, e.g., during treatment of the specific crudeacesulfame potassium compositions discussed herein.

The 5-chloro-acesulfame potassium content may be measured in the crudeand/or finished acesulfame potassium compositions (as well as anyintermediate compositions) via high performance liquid chromatography(HPLC) analysis, based on European Pharmacopoeia guidelines (2017),based on European Pharmacopoeia guidelines for thin layer chromatography(2017) and adapted for HPLC. A particular measurement scenario utilizesan LC Systems HPLC unit from Shimadzu having a CBM-20 Shimadzucontroller and being equipped with a CC 250/4.6 Nucleodur 100-3 C18 ec(250×4.6 mm) MACHEREY NAGEL column. A Shimadzu SPD-M20A photodiode arraydetector can be used for detection (at 234 nm wavelength). Analysis maybe performed at 23° C. column temperature. As an eluent solution, anaqueous solution of tetra butyl ammonium hydrogen sulfate (optionally at3.4 g/L and at 60% of the total solution) and acetonitrile (optionallyat 300 mL/L and at 40% of the total solution) may be employed. Elutionmay be isocratic. The overall flow rate of total eluent may beapproximately 1 mL/min. The data collection and calculations may beperformed using LabSolution software from Shimadzu.

The acetoacetamide-N-sulfonic acid and/or the acetoacetamide content maybe measured in the crude, intermediate, or finished acesulfame potassiumcompositions via HPLC analysis, based on European Pharmacopoeiaguidelines for thin layer chromatography (2017) and adapted for HPLC. Aparticular measurement scenario utilizes an LC Systems HPLC unit fromShimadzu having a CBM-20 Shimadzu controller and being equipped with anIonPac NS1 ((5 μm) 150×4 mm) analytical column and an IonPac NG1 guardcolumn (35×4.0 mm). A Shimadzu SPD-M20A photodiode array detector can beused for detection (at 270 nm and 280 nm wavelength). Analysis may beperformed at 23° C. column temperature. As a first eluent solution, anaqueous mixture of tetra butyl ammonium hydrogen sulfate (3.4 g/L),acetonitrile (300 mL/L), and potassium hydroxide (0.89 g/L) may beemployed; as a second eluent solution, an aqueous mixture of tetra butylammonium hydrogen sulfate (3.4 g/L) and potassium hydroxide (0.89 g/L)may be employed. Elution may be conducted in gradient mode according tothe following second eluent flow profile:

-   -   0 to 3 minutes: constant 80% (v/v)    -   3 to 6 minutes: linear reduction to 50% (v/v)    -   6 to 15 minutes: constant at 50% (v/v)    -   15 to 18 minutes: linear reduction to 0%    -   18 to 22 minutes: constant at 0%    -   22 to 24 minutes: linear increase to 80% (v/v)    -   24 to 35 minutes constant at 80% (v/v).        Overall flow rate of eluent may be approximately 1.2 mL/min. The        data collection and calculations may be performed using        LabSolution software from Shimadzu.

As noted above, the crude acesulfame potassium composition is formed bythe aforementioned contacting of the solvent and the cyclizing agent toform a cyclizing agent composition; cyclic sulfur trioxide adductcomposition formation reaction, and forming from the cyclic sulfurtrioxide adduct the finished acesulfame potassium composition (forexample via hydrolysis, neutralization, and treatment). In preferredembodiments, the contact time may be less than 60 minutes, e.g., lessthan 45 minutes, less than 30 minutes, less than 15 minutes, less than10 minutes, less than 8 minutes, less than 5 minutes, less than 3minutes, or less than 1 minute (optionally ranging from 1 second to 60minutes, e.g., from 1 second to 45 minutes, from 1 second to 30 minutes,from 1 second to 15 minutes, from 1 second to 10 minutes, from 1 minuteto 45 minutes, from 1 minute to 30 minutes, from 1 minute to 15 minutes,from 1 minute to 10 minutes, from 10 seconds to 45 minutes, from 10seconds to 30 minutes, from 30 seconds to 30 minutes, from 1 minute to10 minutes, from 3 minutes to 10 minutes, or from 5 minutes to 10minutes); the crude acesulfame potassium composition may comprise from 1wppb to 35 wppm 5-chloro-acesulfame potassium, e.g., from 1 wppb to 20wppm, from 1 wppb to 10 wppm, from 1 wppb to 5 wppm, from 1 wppb to 2.7wppm, from 10 wppb to 20 wppm, from 10 wppb to 19 wppm, from 10 wppb to15 wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppbto 5 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm, or from100 wppb to 5 wppm (optionally less than 35 wppm 5-chloro-acesulfamepotassium, e.g., less than 30 wppm, less than 25 wppm, less than 20wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than7 wppm, less than 5 wppm, less than 3 wppm, or less than 1 wppm); andthe finished acesulfame potassium composition may comprise from 1 wppbto 35 wppm 5-chloro-acesulfame potassium, e.g., from 1 wppb to 20 wppm,from 1 wppb to 10 wppm, from 1 wppb to 5 wppm, from 1 wppb to 2.7 wppm,from 10 wppb to 20 wppm, from 10 wppb to 19 wppm, from 10 wppb to 15wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppb to5 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm, or from 100wppb to 5 wppm (optionally less than 35 wppm 5-chloro-acesulfamepotassium, e.g., less than 30 wppm, less than 25 wppm, less than 20wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than7 wppm, less than 5 wppm, less than 3 wppm, or less than 1 wppm).

In a particular embodiment, the contact time is less than 15 minutes,the crude acesulfame potassium composition comprises from 0.001 wppm to5 wppm 5-chloro-acesulfame potassium, and the finished acesulfamepotassium composition comprises from 0.001 wppm to 5 wppm5-chloro-acesulfame potassium.

In another particular embodiment, the contact time is less than 5minutes, the crude acesulfame potassium composition comprises from 0.001wppm to 5 wppm 5-chloro-acesulfame potassium, and the finishedacesulfame potassium composition comprises from 0.001 wppm to 2.7 wppm5-chloro-acesulfame potassium.

In another particular embodiment, the contact time ranges from 1 secondto 10 minutes, the crude acesulfame potassium composition comprises from1 wppb to 35 wppm 5-chloro-acesulfame potassium, and the finishedacesulfame potassium composition comprises from 1 wppb to 35 wppm5-chloro-acesulfame potassium.

In another particular embodiment, the contact time ranges from 1 secondto 10 minutes, the crude acesulfame potassium composition comprises from1 wppb to 5 wppm 5-chloro-acesulfame potassium, and the finishedacesulfame potassium composition comprises from 1 wppb to 5 wppm5-chloro-acesulfame potassium.

In another particular embodiment, the contact time ranges from 1 secondto 30 minutes, the crude acesulfame potassium composition comprises from10 wppb to 10 wppm 5-chloro-acesulfame potassium, and the finishedacesulfame potassium composition comprises from 10 wppb to 10 wppm5-chloro-acesulfame potassium.

The acesulfame potassium compositions (crude and/or finished) may, insome cases, comprise other impurities. Exemplary impurities include,inter alia, acetoacetamide, acetoacetamidesulfonate, andacetoacetamide-N-sulfonic acid. The acesulfame potassium compositions(crude and/or finished) also may comprise heavy metals. The organicimpurities and/or heavy metals may be present in an amount ranging from1 wppb to 25 wppm, based on the total weight of the respectiveacesulfame potassium composition, crude or finished, e.g., from 100 wppbto 20 wppm, from 100 wppb to 15 wppm, from 500 wppb to 10 wppm, or from1 wppm to 5 wppm. Heavy metals are defined as metals with relativelyhigh densities, e.g., greater than 3 g/cm³ or greater than 7 g/cm³.Exemplary heavy metals include lead and mercury. In some cases, thecrude or finished acesulfame potassium composition may comprise mercuryin an amount ranging from 1 wppb to 25 wppm, e.g., from 100 wppb to 20wppm, from 100 wppb to 15 wppm, from 500 wppb to 10 wppm, or from 1 wppmto 5 wppm. In terms of limits, the crude or finished acesulfamepotassium composition may comprise less than 25 wppm mercury, e.g., lessthan 20 wppm, less than 15 wppm, less than 10 wppm, or less than 5 wppm.In some cases, the crude or finished acesulfame potassium compositionmay comprise lead in an amount ranging from 1 wppb to 25 wppm, e.g.,from 100 wppb to 20 wppm, from 100 wppb to 15 wppm, from 500 wppb to 10wppm, or from 1 wppm to 5 wppm. In terms of limits, the crude orfinished acesulfame potassium composition may comprise less than 25 wppmlead, e.g., less than 20 wppm, less than 15 wppm, less than 10 wppm, orless than 5 wppm. In some cases, when potassium hydroxide is formed viaa membrane process, the resultant crude or finished acesulfame potassiumcomposition may have very low levels of mercury, if any, e.g., less than10 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than500 wppb, or less than 100 wppb.

In some embodiments, the acesulfame potassium compositions (crude,intermediate, and/or finished) may comprise acetoacetamide-N-sulfonicacid, e.g., less than 37 wppm acetoacetamide-N-sulfonic acid, e.g., lessthan 35 wppm, less than 30 wppm, less than 25 wppm, less than 20 wppm,less than 15 wppm, less than 12 wppm, less than 10 wppm, less than 7wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than0.8 wppm, less than 0.5 wppm, or less than 0.3 wppm. In some cases thefinished acesulfame potassium composition is substantially free ofacetoacetamide-N-sulfonic acid, e.g., free of acetoacetamide-N-sulfonicacid. In terms of ranges, the finished acesulfame potassium compositionmay comprise from 1 wppb to 37 wppm acetoacetamide-N-sulfonic acid,e.g., from 10 wppb to 35 wppm, from 10 wppb to 25 wppm, from 10 wppb to15 wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppbto 7 wppm, from 10 wppb to 5 wppm, from 10 wppb to 3 wppm, from 100 wppbto 15 wppm, from 100 wppb to 10 wppm, or from 100 wppb to 5 wppm.Acetoacetamide-N-sulfonic acid may be formed in side reactions. The useof the aforementioned temperature (and optionally contact time)parameters also provide for low amounts of acetoacetamide-N-sulfonicacid.

In some embodiments, the crude acesulfame potassium composition istreated to achieve the finished acesulfame potassium composition. Insome cases, however, treatment steps may not provide for removal of5-chloro-acesulfame potassium, perhaps due to the chemical similaritiesof 5-chloro-acesulfame potassium and acesulfame potassium. Surprisingly,the use of the process steps disclosed herein advantageously providesfor the reduction or elimination of impurities during the reactionscheme, before purification of the crude acesulfame potassiumcomposition. Accordingly, the need to rely on purification of the crudeacesulfame potassium composition to remove 5-chloro-acesulfame potassiumis beneficially reduced. In some embodiments, the acesulfame potassiumcompositions (crude and/or finished) comprise at least 90% of the5-chloro-acesulfame potassium present the crude acesulfame potassiumcomposition, e.g., at least 93%, at least 95%, or at least 99%.

Intermediate Reaction Parameters

The reactions for production of high purity acesulfame potassium aredescribed in more detail as follows.

Amidosulfamic Acid Salt Formation Reaction

In a first reaction step, sulfamic acid and an amine are reacted to formsulfamic acid salt. An exemplary reaction scheme that employstriethylamine as the amine and yields triethyl ammonium sulfamic acidsalt is shown in reaction (1), below.

H₂N—SO₃H+N(C₂H₅)₃→H₂N—SO₃ ⁻.HN⁺(C₂H₅)₃  (1)

Acetic acid is also present in the first reaction mixture and reactswith the amine, e.g., triethylamine, to form an ammonium acetate, e.g.,triethylammonium acetate, as shown in reaction (2), below.

H₃C—COOH+N(C₂H₅)₃→H₃C—COO⁻. HN⁺(C₂H₅)₃  (2)

The amine employed in these reactions may vary widely. Preferably, theamine comprises triethylamine. In one embodiment, the amine may beselected from the group consisting of trimethylamine,diethylpropylamine, tri-n-propylamine, triisopropylamine,ethyldiisopropylamine, tri-n-butylamine, triisobutylamine,tricyclohexylamine, ethyldicyclohexylamine, N,N-dimethylaniline,N,N-diethylaniline, benzyldimethylamine, pyridine, substituted pyridinessuch as picoline, lutidine, cholidine or methylethylpyridine,N-methylpiperidine, N-ethylpiperidine, N-methylmorpholine,N,N-dimethylpiperazine, 1,5-diazabicyclo[4.3.0]-non-5-en,1,8-diazabicyclo-[5.4.0]-undec-7-en, 1,4-diazabicyclooctane,tetramethylhexamethylendiamine, tetramethylethylendiamine,tetramethylpropylendiamine, tetramethylbutylendiamine,1,2-dimorpholylethan, pentamethyldiethyltriamine,pentaethyldiethylentriamine, pentamethyldipropylentriamine,tetramethyldiaminomethane, tetrapropyldiaminomethane,hexamethyltriethylentetramine, hexamethyltripropylenetetramine,diisobutylentriamine, triisopropylentriamine, and mixtures thereof.

Acetoacetamide Salt Formation Reaction

Once formed in reaction (1), the sulfamic acid salt is reacted with theacetoacetylating agent to form the acetoacetamide salt, preferablyacetoacetamide-N-sulfonate triethylammonium salt. Preferably, theacetoacetylating agent comprises diketene, although otheracetoacetylating agents may be employed, either with or withoutdiketene.

In one embodiment, the resultant acetoacetamide salt corresponds to thefollowing formula (3).

wherein M⁺ is an appropriate ion. Preferably, M⁺ is an alkali metal ionor N⁺R₁R₂R₃R₄. R₁, R₂, R₃ and R₄, independently of one another, may beorganic radicals or hydrogen, preferably H or C₁-C₈ alkyl, C₆-C₁₀cycloalkyl, aryl and/or aralkyl. In a preferred embodiment, R₁ ishydrogen, and R₂, R₃ and R₄ are alkyl, e.g., ethyl.

An exemplary reaction scheme for forming an acetoacetamide salt employsa trialkyl ammonium amidosulfamic acid salt and diketene as reactantsand yields an acetoacetamide triethylammonium salt is shown in reaction(4), below.

In one embodiment, the reaction is conducted in the presence of acatalyst, which may vary widely. In some embodiments, the catalystcomprises one or more amines and/or phosphines. Preferably, the catalystcomprises triethylamine. In some cases trimethylamine serves as both acatalyst and a reactant.

In one embodiment wherein the amidosulfamic acid salt formation reactionand the acetoacetamide salt formation reaction are conducted in separatereactors, a second reaction mixture comprises the amidosulfamic acidsalt, the diketene, and the catalyst, e.g., triethylamine. Preferably,catalyst from the first reaction is carried through to the reactionmixture of the second reaction. The second reaction mixture is thensubjected to conditions effective to form the acetoacetamide salt.

In one embodiment, the composition of the second reaction mixture may besimilar to that of the first reaction mixture. In a preferredembodiment, the reaction product of the amidosulfamic acid saltformation reaction provides the amidosulfamic acid salt component of thesecond reaction mixture. In addition to the above-mentioned components,the second reaction mixture may further comprise reaction by-productsfrom the first reaction or non-reacted starting materials.

In one embodiment, the amount of acetoacetylating agent, e.g., diketene,should be at least equimolar to the reactant amidosulfamic acid saltthat is provided. In one embodiment, the process may utilize a diketenein excess, but preferably in an excess less than 30 mol %, e.g., lessthan 10 mol %. Greater excesses are also contemplated.

The amidosulfamic acid salt formation reaction and/or the acetoacetamidesalt formation reaction may employ an organic solvent. Suitable inertorganic solvents include anyorganic solvents that do not react in anundesired manner with the starting materials, cyclizing agent, finalproducts and/or the catalysts in the reaction. The solvents preferablyhave the ability to dissolve, at least partially, amidosulfamic acidsalts. Exemplary organic solvents include halogenated aliphatichydrocarbons, preferably having up to 4 carbon atoms such as, forexample, methylene chloride, chloroform, 1,2-dichlorethane,trichloroethylene, tetrachloroethylene, trichlorofluoroethylene;aliphatic ketones, preferably those having 3 to 6 carbon atoms such as,for example, acetone, methyl ethyl ketone; aliphatic ethers, preferablycyclic aliphatic ethers having 4 or 5 carbon atoms such as, for example,tetrahydrofuran, dioxane; lower aliphatic carboxylic acids, preferablythose having 2 to 6 carbon atoms such as, for example, acetic acid,propionic acid; aliphatic nitriles, preferably acetonitrile;N-alkyl-substituted amides of carbonic acid and lower aliphaticcarboxylic acids, preferably amides having up to 5 carbon atoms such as,for example, tetramethylurea, dimethylformamide, dimethylacetamide,N-methylpyrrolidone; aliphatic sulfoxides, preferably dimethylsulfoxide, and aliphatic sulfones, preferably sulfolane.

Particularly preferred solvents include dichloromethane (methylenechloride), 1,2-dichloroethane, acetone, glacial acetic acid anddimethylformamide, with dichloromethane (methylene chloride) beingparticularly preferred. The solvents may be used either alone or in amixture. In one embodiment, the solvent is a halogenated, aliphatichydrocarbon solvent, preferably the solvent is dichloromethane.Chloroform and tetrachloromethane are also exemplary solvents.

In one embodiment, the acetoacetamide salt formation reaction isconducted a temperature ranging from −30° C. to 50° C., e.g., from 0° C.to 25° C. The reaction pressure may vary widely. In preferredembodiments, the reaction is carried out at atmospheric pressure,although other pressures are also contemplated. The reaction time mayvary widely, preferably ranging from 0.5 hours to 12 hours, e.g., from 1hour to 10 hours. In one embodiment, the reaction is carried out byintroducing the amidosulfamic acid salt and metering in the diketene. Inanother embodiment, the reaction is carried out by introducing diketeneand metering in the amidosulfamic acid salt. The reaction may be carriedout by introducing the diketene and amidosulfamic acid and metering inthe catalyst.

Once formed, each reaction product is optionally subjected to one ormore purification steps. For example, the solvent may be separated fromthe reaction product, e.g., via distillation, and the residue (mainlyacetoacetamide-N-sulfonate) may be recrystallized from a suitablesolvent such as, for example, acetone, methyl acetate or ethanol.

Generally speaking, the steps of reacting sulfamic acid andtriethylamine to form an amidosulfamic acid salt, reacting theamidosulfamic acid salt and diketene to form the acetoacetamide salt,and contacting dichloromethane and a sulfur trioxide to form a cyclizingagent composition are performed in no particular order. Each of thesesteps may be performed independently of one another. In some cases,these steps may be performed in any order as long as they are performedbefore the cyclization reaction, e.g., the reaction of theacetoacetamide salt with sulfur trioxide to form a cyclic sulfurtrioxide adduct.

Cyclization and Hydrolyzation

The acetoacetamide salt is reacted with cyclizing agent, e.g., cyclizingagent in the cyclizing agent composition, in the presence of a solventto form the cyclic (sulfur trioxide) adduct composition, which containscyclic sulfur trioxide adduct and, in some cases, impurities. In somecases, a cooling step occurs before the cyclic sulfur trioxide adductformation reaction. In one embodiment, the cyclization is achieved byusing at least an equimolar amount of the cyclizing agent. The cyclizingagent may be dissolved in an inert inorganic or organic solvent. Thecyclizing agent is generally used in a molar excess, e.g., up to a 20fold excess, or up to a 10 fold excess, based on the total moles ofacetoacetamide salt. An exemplary cyclization reaction using sulfurtrioxide as the cyclizing agent is shown in reaction (5), below.

In one embodiment, the weight ratio of solvent to cyclizing agent in thecyclizing agent composition is at least 1:1, e.g., at least 2:1, or atleast 5:1. In one embodiment, the weight ratio of solvent to cyclizingagent in the cyclizing agent composition ranges from 1:1 to 25:1, e.g.,from 1:1 to 10:1, from 2:1 to 10:1, or from 5:1 to 10:1.

A cyclizing agent may be any compound that initiates the ring closure ofthe acetoacetamide salt. Although sulfur trioxide is a preferredcyclizing agent, the employment of other cyclizing agents iscontemplated.

Suitable inert inorganic or organic solvents are those liquids which donot react in an undesired manner with sulfur trioxide or the startingmaterials or final products of the reaction. Preferred organic solventsinclude, but are not limited to, halogenated aliphatic hydrocarbons,preferably having up to four carbon atoms, such as, for example,methylene chloride (dichloromethane), chloroform, 1,2-dichloroethane,trichloroethylene, tetrachloroethylene, trichlorofluoroethylene; estersof carbonic acid with lower aliphatic alcohols, preferably with methanolor ethanol; nitroalkanes, preferably having up to four carbon atoms, inparticular nitromethane; alkyl-substituted pyridines, preferablycollidine; and aliphatic sulfones, preferably sulfolane. Particularlypreferred solvents for the cyclization reaction include dichloromethane(methylene chloride), 1,2-dichloroethane, acetone, glacial acetic acidand dimethylformamide, with dichloromethane (methylene dichloride) beingparticularly preferred. Other solvents, e.g., other solvents mentionedherein, may also be suitable as solvents. The solvents may be usedeither alone or in a mixture. In one embodiment, the solvent is ahalogenated, aliphatic hydrocarbon solvent, preferably the solvent isdichloromethane. The processes may employ these solvents alone or inmixtures thereof.

In some cases, the solvent in the cyclizing agent composition may beselected from 1) concentrated sulfuric acid, 2) liquid sulfur dioxide,or 3) an inert organic solvent.

In a preferred embodiment, the same solvent is used in both theacetoacetamide salt formation reaction and the cyclization reaction. Asone benefit, the solution obtained in the acetoacetamide salt formationreaction, without isolation of the acetoacetamide salt formationreaction product, may be used immediately in the cyclization.

In one embodiment, the reaction temperature for the cyclization reactionranges from −70° C. to 175° C., e.g., from −40° C. to 60° C. Thepressure at which the reaction is conducted may vary widely. In oneembodiment, the reaction is conducted at a pressure ranging from 0.01MPa to 10 MPa, e.g., from 0.1 MPa to 5 MPa. Preferably, the reaction isconducted at atmospheric pressure.

The acetoacetamide salt may be introduced to the cyclization reactor andthe cyclizing agent composition, e.g., a solution of cyclizing agentoptionally in solvent, may be metered into the reactor. In preferredembodiments, both reactants (acetoacetamide salt and cyclizing agent)are simultaneously fed into the reactor. In one embodiment, thecyclizing agent composition is initially introduced into the reactor andthe acetoacetamide salt is added. Preferably, at least part of thecyclizing agent composition is introduced into the reactor and, eithercontinuously or in portions, acetoacetamide salt and (additional)cyclizing agent are then metered in, preferably while maintaining thetemperature as described above.

The acetoacetamide salt may be introduced to the reactor and thecyclizing agent composition may be metered into the reactor. Inpreferred embodiments, both reactants are simultaneously fed into thereactor. In one embodiment, the cyclizing agent composition is initiallyintroduced into the reactor and the acetoacetamide salt is added.Preferably, at least part of the cyclizing agent composition isintroduced into the reactor and, either continuously or in portions,acetoacetamide salt and (additional) cyclizing agent are then meteredin, preferably while maintaining the temperature as described above.

The formation of the crude acesulfame potassium composition from thecyclic sulfur trioxide adduct composition, in some embodiments,comprises the steps of hydrolyzing the cyclic sulfur trioxide adduct toform an acesulfame-H composition; neutralizing the acesulfame-H in theacesulfame H composition to form a crude acesulfame potassiumcomposition; and forming the acesulfame potassium composition from thecrude acesulfame potassium composition.

The cyclic sulfur trioxide adduct may be hydrolyzed via conventionalmeans, e.g., using water. Thus, the forming step may comprise the stepsof hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-Hcomposition. Acesulfame-H is referred to as sweetener acid.

An exemplary hydrolysis reaction scheme is shown in reaction (6), below.

The addition of the water leads to a phase separation. The majority ofthe sweetener acid, acesulfame-H(6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one 2,2-dioxide), which isformed via the hydrolysis, is present in the organic phase, e.g., atleast 60 wt %, at least 70%, at least 80%, or at least 90%. Theremainder of the sweetener acid is in the water phase and can beextracted and optionally added to the sweetener acid in the organicphase. In cases where dichloromethane is used as the reaction medium,water or ice may be added, e.g., in a molar excess, based on the sulfurtrioxide, to the cyclic sulfur trioxide adduct/sulfur trioxide solution.

In some cases, the hydrolysis step comprises adding water to the cyclicsulfur trioxide adduct. In preferred embodiments, the weight ratio ofwater to acetoacetamide salt is greater than 1.3:1, e.g., greater than1.5:1, greater than 1.7:1, greater than 2:1 or greater than 2.2:1.Employment of these ratios may lead to decreases inacetoacetamide-N-sulfonic acid and/or acetoacetamide formation in theneutralized crude acesulfame potassium composition, e.g., the crudeacesulfame potassium composition may comprise acetoacetamide-N-sulfonicacid in the amounts discussed herein.

It was surprisingly discovered that the temperature at which the wateris initially fed to the hydrolysis reaction may have beneficial effectson impurity production, e.g., organic production or 5-chloro-acesulfamepotassium production as well as reaction parameters, e.g., temperature.At lower temperatures, e.g., lower than approximately −35° C. or lowerthan −22° C., ice tends to build up in the reaction mixture. As this icemelted, it led to the onset of additional reaction, which caused thetemperature to rise quickly. This rise in temperature surprisingly ledto a product that contained much higher levels of impurities. In somecases, the hydrolyzing comprises adding hydrolysis water to the cyclicsulfur trioxide adduct to form a hydrolysis reaction mixture andreacting the mixture to from the acesulfame-H composition. In someembodiments, the temperature of the hydrolysis reaction mixture or thetemperature at which the hydrolysis water is fed to the reactor ismaintained at a temperature greater than −35° C., e.g., greater than−30° C., greater than −25° C., greater than −24° C., greater than −23°C., greater than −22° C., greater than −21.5° C., greater than −21° C.,or greater than greater than −20° C. In terms of ranges, the temperatureof the hydrolysis reaction mixture or the temperature at which thehydrolysis water is fed to the reactor optionally is maintained at atemperature ranging from −35° C. to 0° C., e.g., from −30° C. to −5° C.,from −20° C. to −5° C., from −30° C. to −20° C., from −25° C. to −21°C., or −25° C. to −21.5° C.

After the addition of water, the reaction solvent, e.g.,dichloromethane, may be removed by distillation, or the acesulfame-Hthat remains in the organic phase may be extracted with a more suitablesolvent. Suitable solvents are those which are sufficiently stabletowards sulfuric acid and which have a satisfactory dissolving capacity.Other suitable solvents include esters of carbonic acid such as, forexample dimethyl carbonate, diethyl carbonate and ethylene carbonate, oresters of organic monocarboxylic acids such as, for example, isopropylformate and isobutyl formate, ethyl acetate, isopropyl acetate, butylacetate, isobutyl acetate and neopentyl acetate, or esters ofdicarboxylic acids or amides which are immiscible with water, such as,for example, tetrabutylurea, are suitable. Isopropyl acetate andisobutyl acetate are particularly preferred.

The combined organic phases are dried with, for example, Na₂SO₄, and areevaporated. Any sulfuric acid which has been carried over in theextraction may be removed by appropriate addition of aqueous alkali tothe organic phase. For this purpose, dilute aqueous alkali may be addedto the organic phase until the pH reached in the aqueous phasecorresponds to that of pure 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one2,2-dioxide at the same concentration in the same two-phase system ofextracting agent and water.

Neutralization

The neutralization of the acesulfame-H yields a non-toxic salt ofacesulfame-H, e.g., acesulfame potassium. In one embodiment,neutralization is carried out by reacting the acesulfame-H with anappropriate base, e.g., potassium hydroxide, in particular amembrane-produced potassium hydroxide. Other suitable bases include, forexample, KOH, KHCO₃, K₂CO₃, and potassium alcoholates. An exemplaryreaction scheme using potassium hydroxide as a neutralizing agent isshown in reaction (7), below.

In some cases, the neutralization is conducted or maintained at a low pHlevels, which may advantageously further result in a reduction orelimination of the formation of impurities, e.g., acetoacetamide salts.In this context, “conducted” means that the neutralization step beginsat a low pH level, and “maintained” means that steps are taken to ensurethat the pH stays within a low pH range throughout the entireneutralization step. In one embodiment, the neutralization step isconducted or maintained at a pH below 10.0, e.g., below 9.5, below 9.0,below 8.5, below 8.0, below 7.5, below 7.0, or below 6.5. In terms ofranges, the neutralization step is preferably conducted or maintained ata pH between 6.0 and 10.0, e.g., between 6.5 and 9.5, between 7.0 and9.0, or between 7.5 and 8.5.

In some cases, the pH in the neutralizing step may be maintained withinthe desired range by managing the components of the neutralizationreaction mixture, which comprises acesulfame-H and neutralizing agent(and also solvent). For example, the composition of the neutralizationreaction mixture may include from 1 wt % to 95 wt % neutralizing agent,e.g., from 10 wt % to 85 wt % or from 25 wt % to 75 wt %, and from 1 wt% to 95 wt % acesulfame-H, e.g., from 10 wt % to 85 wt % or from 25 wt %to 75 wt %. These concentration ranges are based on the mixture ofneutralization agent and acesulfame-H (not including solvent).

In one embodiment, the acesulfame-H may be neutralized and extracteddirectly from the purified organic extraction phase using an aqueouspotassium base. The acesulfame potassium then precipitates out, whereappropriate after evaporation of the solution, in the crystalline form,and it can also be recrystallized for purification.

In one embodiment, the process is not a small-scale batch process or alaboratory-scale process. For example, the inventive process forproducing a finished acesulfame potassium composition may yield at least50 grams of finished acesulfame potassium composition per batch, e.g.,at least 100 grams per batch, at least 500 grams per batch, at least 1kilogram per batch, or at least 10 kilograms per batch. In terms ofrates, the inventive process may yield at least 50 grams of finishedacesulfame potassium composition per hour, e.g., at least 100 grams perhour, at least 500 grams per hour, at least 1 kilogram per hour, or atleast 10 kilograms per hour.

FIG. 1 shows an exemplary acesulfame potassium process 100 in accordancewith the process described herein. Process 100 comprises amidosulfamicacid salt formation reactor 102 and acetoacetamide salt formationreactor 104. Although FIG. 1 shows separate reactors for the twointermediate formation reactions, other configurations, e.g., a onereactor process, are within the contemplation of the present process.Sulfamic acid is fed to amidosulfamic acid salt formation reactor 102via sulfamic acid feed line 106. One or more amines, preferablytriethylamine, are fed to amidosulfamic acid salt formation reactor 102via amine feed line 108. In addition to sulfamic acid and amine(s),acetic acid is also fed to amidosulfamic acid salt formation reactor 102(via feed line 110). The resultant reaction mixture in amidosulfamicacid salt formation reactor 102 is as discussed above. In amidosulfamicacid salt formation reactor 102, the sulfamic acid and the amine (in thepresence of the acetic acid) are reacted to yield a crude amidosulfamicacid salt composition, which exits reactor 102 via line 112. Althoughnot shown, a reaction solvent, e.g., dichloromethane may also be presentin the amidosulfamic acid salt formation reactor 102.

The crude amidosulfamic acid salt composition in line 112 is directed toacetoacetamide salt formation reactor 104. Diketene is fed toacetoacetamide salt formation reactor 104 via feed line 114. Inacetoacetamide salt formation reactor 104, the amidosulfamic acid saltand the diketene are reacted to yield a crude acetoacetamide saltcomposition, which exits reactor 104 via line 118. Although not shown,dichloromethane may also be present in the acetoacetamide salt formationreactor 104.

Cyclizing agent (sulfur dioxide) and solvent (dichloromethane) are fedto vessel 119 via feed lines 121 and 123. Vessel 119 is preferably acooling vessel wherein the cyclizing agent composition (as discussedabove) is formed. The cyclizing agent composition exits vessel 119 vialine 125.

The crude acetoacetamide salt composition is directed to cyclizationreactor 120 via line 118. The cooled cyclizing agent composition is alsodirected to cyclization reactor 120 (via line 125). Line 125 ispreferably made of a material and in such a size and shape to facilitatethe residence times discussed herein. In cyclization reactor 120, theacetoacetamide salt in the crude acetoacetamide salt composition in line118 is cyclized and a cyclic sulfur trioxide adduct stream exits vialine 124.

The cyclic sulfur trioxide adduct in line 124, is directed to hydrolysisreactor 126. Water is fed to hydrolysis reactor 126 via water feed 128.In hydrolysis reactor 126, the cyclic sulfur trioxide adduct ishydrolyzed to yield a crude acesulfame-H composition, which exitshydrolysis reactor 126 via line 130 and is directed to phase separationunit 132. Phase separation unit 132 separates the contents of line 130into organic phase 134 and aqueous phase 136. Organic phase 134comprises a major amount of the acesulfame-H in line 130 as well assolvent, e.g., methylene chloride. Aqueous phase 136 exits via line 137and comprises triethylammonium sulfate, and optionally sulfuric acid andminor amounts of acesulfame-H. This aqueous phase may be furtherpurified to separate and/or recover the acesulfame-H and/or thetriethylammonium sulfate. The recovered acesulfame-H may be combinedwith the acesulfame from the organic phase (not shown).

Organic phase 134 exits phase separation unit 132 and is directed toextraction column 138 (via line 140). Water is fed to extraction column138 via water feed 142. The water extracts residual sulfates from thecontents of line 140 and a purified acesulfame-H composition exitsextraction column 138 via line 144. The extracted sulfates exitextraction column 138 via line 145.

The organic phase exits phase separation unit 132 and is directed toextraction column 138 (via line 140). Water is fed to extraction column138 via water feed 142. The water extracts residual sulfates from thecontents of line 140 and a purified acesulfame-H stream exits extractioncolumn 138 via line 144. The extracted sulfates exit extraction column138 via line 145.

The purified acesulfame-H composition in line 144 is directed toneutralization unit 146. Potassium hydroxide is also fed toneutralization unit 146 (via line 148). The potassium hydroxideneutralizes the acesulfame-H in the purified acesulfame-H composition toyield a product comprising acesulfame potassium, dichloromethane, water,potassium hydroxide, and impurities, e.g., 5-chloro-acesulfamepotassium, which exits neutralization unit 146 via line 150. Thisproduct may be considered a crude acesulfame potassium composition.

The product in line 150 is directed to phase separation unit 160. Phaseseparation unit 160 separates the product in line 150 into organic phase162 and an aqueous phase 164. Aqueous phase 164 comprises a major amountof the acesulfame potassium in line 150 as well as some impurities.Organic phase 162 comprises potassium hydroxide, dichloromethane, andwater and may be further treated to recover these components. Aqueousphase 164 (without any further treatment) may be considered a crudeacesulfame potassium composition. Aqueous phase 164 may be optionallytreated to form a finished acesulfame potassium composition.

Aqueous phase 164 is directed to treatment unit 156 via line 166. Intreatment unit 156, aqueous phase 164 is treated to obtain finishedacesulfame potassium composition (product that may be sold), which isshown exiting via stream 152. In addition to the finished acesulfamepotassium composition, dichloromethane and potassium hydroxide may beseparated. These components exit treatment unit 156 via line 154. Thecontents of stream 154 may be recovered and/or recycled to the process.

The crude acesulfame potassium product stream comprises acesulfamepotassium, dichloromethane, water, and potassium hydroxide. The crudeacesulfame potassium product stream in line 150 may be directed tofurther processing to recover purified acesulfame potassium, which isshown exiting via stream 152. In addition to the purified acesulfamepotassium, dichloromethane and potassium hydroxide may be separated fromthe crude acesulfame potassium product stream, as shown by stream 154.The contents of stream 154 may be recovered and/or recycled to theprocess.

The invention relates also to the following aspects:

Aspect 1: A process for producing a finished acesulfame potassiumcomposition, the process comprising the steps of:

(a) contacting a solvent and a cyclizing agent to form a cyclizing agentcomposition;

(b) reacting an acetoacetamide salt with the cyclizing agent in thecyclizing agent composition to form a cyclic sulfur trioxide adduct; and

(c) forming from the cyclic sulfur trioxide adduct the finishedacesulfame potassium composition comprising non-chlorinated acesulfamepotassium and less than 35 wppm 5-chloro-acesulfame potassium;

wherein contact time from the beginning of step (a) to the beginning ofstep (b) is less than 60 minutes.

Aspect 2: The process of aspect 1, wherein the forming comprises:

hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-Hcomposition comprising acesulfame-H;

neutralizing the acesulfame-H in the acesulfame-H composition to form acrude acesulfame potassium composition comprising non-chlorinatedacesulfame potassium and less than 35 wppm 5-chloro-acesulfamepotassium; and

-   -   forming the finished acesulfame potassium composition from the        crude acesulfame potassium composition.

Aspect 3: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to 5wppm 5-chloro-acesulfame potassium.

Aspect 4: The process of any one of the preceding aspects, wherein thecontact time is less than 15 minutes and the crude acesulfame potassiumcomposition comprises from 0.001 wppm to 5 wppm 5-chloro-acesulfamepotassium and the finished acesulfame potassium composition comprisesfrom 0.001 wppm to 5 wppm 5-chloro-acesulfame potassium.

Aspect 5: The process of any one of the preceding aspects, wherein thecontact time is less than 5 minutes and the crude acesulfame potassiumcomposition comprises from 0.001 wppm to 5 wppm 5-chloro-acesulfamepotassium and the finished acesulfame potassium composition comprisesfrom 0.001 wppm to 2.7 wppm 5-chloro-acesulfame potassium.

Aspect 6: The process of any one of the preceding aspects, wherein thecrude acesulfame potassium composition comprises less than 35 wppm5-chloro-acesulfame potassium.

Aspect 7: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises at least 90% byweight of the 5-chloro-acesulfame potassium present in the crudeacesulfame potassium composition.

Aspect 8: The process of any one of the preceding aspects, wherein thehydrolyzing comprises adding water to the cyclic sulfur trioxide adductto form a hydrolysis reaction mixture, and wherein the temperature ofthe hydrolysis reaction mixture is maintained at a temperature rangingfrom −35° C. to 0° C.

Aspect 9: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to 5wppm organic impurities.

Aspect 10: The process of any one of the preceding aspects, furthercomprising:

reacting sulfamic acid and an amine to form an amidosulfamic acid salt;and

reacting the amidosulfamic acid salt and acetoacetylating agent to formthe acetoacetamide salt.

Aspect 11: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to2.7 wppm 5-chloro-acesulfame potassium.

Aspect 12: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to 5wppm organic impurities.

Aspect 13: The process of any one of the preceding aspects, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to 5wppm heavy metals.

Aspect 14: The process of any one of the preceding aspects, wherein thecyclizing agent composition comprises less than 1 wt % of compoundsselected from chloromethyl chlorosulfate, methyl-bis-chlorosulfate, andmixtures thereof.

Aspect 15: The process of any one of the preceding aspects, wherein thereacting is conducted for a cyclization reaction time, from the start ofthe reactant feed to the end of the reactant feed, less than 35 minutes.

Aspect 16: The process of any one of the preceding aspects, wherein theweight ratio of solvent to cyclizing agent in the cyclizing agentcomposition is at least 1:1.

Aspect 17: The process of any one of the preceding aspects, furthercomprising cooling the cyclizing agent composition to a temperature lessthan 15° C.

Aspect 18: The process of any one of the preceding aspects, wherein thecyclizing agent comprises sulfur trioxide and the solvent comprisesdichloromethane.

Aspect 19: A finished acesulfame potassium composition produced orproducible by, or obtainable or obtained from the process of any one ofaspects 1 to 18.

Aspect 20: The finished acesulfame potassium composition of aspect 19,comprising:

non-chlorinated acesulfame potassium;

from 0.001 wppm to 2.7 wppm 5-chloro acesulfame potassium; and

from 0.001 wppm to 5 wppm heavy metals.

Aspect 21: A process for producing a finished acesulfame potassiumcomposition, the process comprising the steps of:

reacting sulfamic acid and triethylamine to form an amidosulfamic acidsalt;

reacting the amidosulfamic acid salt and diketene to form theacetoacetamide salt;

contacting dichloromethane and a sulfur trioxide to form a cyclizingagent composition; reacting the acetoacetamide salt with the sulfurtrioxide in the cyclizing agent composition to form a cyclic sulfurtrioxide adduct;

hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-Hcomposition;

and neutralizing the acesulfame-H to form the finished acesulfamepotassium composition comprising non-chlorinated acesulfame potassiumand less than 10 wppm 5-chloro-acesulfame potassium,

wherein contact time from the beginning of step (a) to the beginning ofstep (b) is less than 10 minutes.

Aspect 22: The process of aspect 21, further comprising cooling thecyclizing agent composition to a temperature less than 15° C.

Aspect 23: An acesulfame potassium composition comprisingnon-chlorinated acesulfame potassium and less than 35 wppm, preferably0.001 wppm to 2.7 wppm 5-chloro-acesulfame potassium.

Aspect 24: The acesulfame potassium composition of aspect 23, furthercomprising less than 37 wppm, preferably 1 wppb to 5 wppmacetoacetamide-N-sulfonic acid.

Aspect 25: The acesulfame potassium composition of any one of thepreceding aspects, further comprising 0.001 wppm to 5 wppm organicimpurities and/or 0.001 wppm to 5 wppm of at least one heavy metal.

Aspect 26: The acesulfame potassium composition of any one of thepreceding aspects, wherein the at least one heavy metal is selected fromthe group consisting of mercury, lead and both.

Aspect 27: The acesulfame potassium composition of any one of thepreceding aspects, wherein the mercury is present in an amount of 1 wppbto 20 wppm.

Aspect 28: The acesulfame potassium composition of any one of thepreceding aspects, wherein the lead is present in an amount of 1 wppb to25 wppm.

EXAMPLES Example 1

Liquid sulfur trioxide and dichloromethane were continuously fed,contacted (to form a cyclizing agent composition), and cooled into astatic mixer at 1220 kg/h and 8000 kg/h, respectively. The temperatureof the cooled cyclizing agent composition was 11° C. The mixture washeld in the static mixture for less than 5 minutes and then fed into acyclization reactor, thus contact time was less than 5 minutes. In thecyclization reactor the sulfur trioxide/diclhloromethane composition wasreacted with a solution of acetoacetamide-N-sulfonate triethylammoniumsalt (acetoacetamide salt) in dichloromethane. The resultant cyclizedproduct was hydrolyzed and worked up to yield a crude acesulfamepotassium composition comprising (non-chlorinated) acesulfame potassium.Testing for 5-chloro-acesulfame potassium content was performed usingthe HPLC equipment and techniques discussed herein. In particular, theHPLC analysis was performed using an LC Systems HPLC unit from Shimadzuhaving a CBM-20 Shimadzu controller and being equipped with a CC 250/4.6Nucleodur 100-3 C18 ec (250×4.6 mm) MACHEREY NAGEL column. A ShimadzuSPD-M20A photodiode array detector was used for detection (at 234 nmwavelength). Analysis was performed at 23° C. column temperature. As aneluent solution, an aqueous solution of tetra butyl ammonium hydrogensulfate (3.4 g/L and 60% of the total solution) and acetonitrile (HPLCgrade) (300 mL/L and 40% of the total solution) was employed. Elutionwas isocratic. The overall flow rate of total eluent was approximately 1mL/min. The data collection and calculations were performed usingLabSolution software from Shimadzu. With a detection limit of 1 wppm, no5-chloro-acesulfame potassium was detected.

Comparative Example A

528 mmol of sulfur trioxide in dichloromethane was prepared and storedfor 20 days at 20° C. The sulfur trioxide/diclhloromethane compositionwas fed to a stirred vessel. 100 mmol acetoacetamide-N-sulfonatetriethylammonium salt in dichloromethane was reacted with the sulfurtrioxide/diclhloromethane composition by continuous feeding into thestirred vessel for 30 minutes. Contact time was 20 days. Afteradditional stirring for two minutes, the reaction mixture was hydrolyzedby the addition of 50 ml water and worked up as described herein.Testing for 5-chloro-acesulfame potassium content was performed usingthe HPLC equipment and techniques discussed above. The crude acesulfamepotassium had an impurity content of 4960 wppm 5-chloro-acesulfamepotassium.

Example 2 and Comparative Examples B and C

100 mmol of 99.5% pure sulfamic acid was suspended in 50 mLdichloromethane in a flask with reflux. Under continuous agitation, 105mmol of trimethylamine was added within approximately 3 minutes. Duringthis time, temperature increased due to acid/base exothermal reaction upto about 42° C. (the boiling point of dichloromethane). This reactionmixture was stirred for approximately 15 additional minutes, until nosolid sedimentation was seen in the flask. Then, 10 mmol of acetic acidwas added to the first reaction mixture and was stirred forapproximately 15 additional minutes. At this point, within 7 minutes ofthe addition of the acetic acid, 110 mmol of diketene was added dropwiseto form a second reaction mixture. After the addition of all of thediketene was added to the second reaction mixture and approximately 15minutes of reaction time, this second reaction mixture was cooled. Theresultant cooled second reaction mixture contained approximately 30%acetoacetamide N-sulfonate triethylammonium salt. Additional batches ofcooled second reaction mixture were prepared as necessary. Theacetoacetamide N-sulfonate triethylammonium salt was used as discussedbelow.

Sulfur trioxide/dichloromethane compositions (cyclizing agentcompositions) were prepared by contacting approximately 15 wt % sulfurtrioxide and approximately 85 wt % dichloromethane with one another in aflask.

For each of Example 2 and Comparative Examples B and C, a reaction flask(a 4 necked round bottom flask equipped with mechanical stirrer,thermometer, and feed vessels) was placed into a cooling bath containinga mixture of isopropanol and dry ice. Approximately 200 g of theacetoacetamide-N-sulfonate triethylammonium salt solution andapproximately 577 g of the sulfur trioxide/dichloromethane compositionswere measured. The compositions were held for various time periodsbefore the start of the cyclization reaction. Contact times for therespective examples are shown in Table 1.

TABLE 1 Contact Times Example Contact Time Ex. 2 1 hour Comp. Ex. B 4days Comp. Ex. C 5 days

For each example, the flask was placed into a cooling bath containing amixture of isopropanol and dry ice. Approximately 15 wt % of the totalsulfur trioxide/dichloromethane composition (approximately 87 g) wasinitially fed to the reaction flask under continuous agitation bymechanical stirrer. When the temperature of the reaction flask contentsreached −35° C. (due to the cooling batch), the remainder of the sulfurtrioxide/dichloromethane composition and all of theacetoacetamide-N-sulfonate triethylammonium salt solution were fed intothe reaction flask. The time period that the solvent contacted thecyclizing agent before formation of the cyclic sulfur trioxide adduct,e.g., before the acetoacetamide-N-sulfonate triethylammonium saltsolution was fed to the reaction flask, was less than an hour. The feedrate was controlled in such a way that the temperature of the reactionflask contents remained between −25° and −35° C. during thefeeding/cyclization reaction. After the reactants were fed, the reactionwas allowed to proceed for approximately one additional minute. Thecooling bath was then removed.

After approximately one minute, the temperature of the reaction flaskcontents reached approximately −22° C. At this time, hydrolysis wasinitiated by feeding deionized water to the reaction flask. Water wasfed over 10 minutes. The hydrolysis reaction was exothermic. Water wasadded slowly so as to maintain temperature between −20° C. and −5° C.After addition of water, reaction mixture was allowed to reach roomtemperature.

The hydrolyzed product was phase separated via a separating funnel. Aheavier organic sweetener acid-dichloromethane phase (acesulfame-Hcomposition) was separated out, and the remaining aqueous phase wasdiscarded.

The acesulfame-H in the acesulfame-H composition was neutralized with a10% potassium hydroxide solution. Neutralization was carried out at 25°C.±1° C. Potassium hydroxide addition was completed within 20 minutes.

After completion of the neutralization step, an additional phaseseparation was performed using a separating funnel to yield an aqueousphase containing acesulfame potassium (and some impurities) and anorganic phase. The aqueous phase is considered a crude acesulfamepotassium composition. The aqueous phase analyzed for impurities, e.g.,5-chloro acesulfame potassium. Testing for 5-chloro-acesulfame potassiumcontent was performed using the HPLC equipment and techniques discussedabove. The remaining dichloromethane phase was discarded.

The results of the impurity analysis of Examples 1 and 2 and ComparativeExamples A-C are shown in Table 2.

TABLE 2 5-chloro Ace-K Content 5-chloro Contact Ace-K (in Time crude),wppm Ex. 1 <5 min. Not detectable Ex. 2 1 hour 32 Comp. Ex. A 20 days4960 Comp. Ex. B 4 days 54 Comp. Ex. C 5 days 78

As shown in the Examples, the 5-chloro-acesulfame potassium content wasaffected by contact time. When a contact time of greater than 1 hour wasemployed (Comparative Examples A-C), significant amounts of 5-chloroacesulfame potassium were present in the crude acesulfame potassiumcomposition. Importantly, when contact time was kept below 1 hour(Example 2), e.g., below 5 minutes (Example 1), then crude acesulfamepotassium composition comprised much smaller amounts of 5-chloroacesulfame potassium.

Only minor and simple additional treatment of the crude acesulfamecomposition was necessary to form the finished acesulfame potassiumcompositions.

Approximately 50% of water was evaporated out of the crude acesulfamepotassium compositions in roti vapor at reduced pressure. The resultantconcentrated acesulfame potassium composition is considered anintermediate acesulfame potassium composition and was then cooled in arefrigerator at +5° C., which led to precipitation of crude crystalscontaining mostly acesulfame potassium.

The crude crystals were then dissolved in enough water and thisresultant solution was heated to 70° C. Activated carbon powder was thenadded to the solution. The solution (with the added activated carbon)was then filtered.

The filtrate that was yielded from the filtration was cooled to roomtemperature, which led to the formation of crystals containing mostlyacesulfame potassium. These crystals were dissolved in sufficient waterand heated to 70° C. in a water bath.

Activated carbon was added to this solution of crystals and activatedcarbon. This solution was then filtered. When filtrate was cooled downto room temperature, white-colored crystals of acesulfame potassium wereformed. These crystals are considered a finished acesulfame potassiumcomposition.

Testing for 5-chloro-acesulfame potassium content was performed usingthe HPLC equipment and techniques discussed above. The crystals of thefinished acesulfame potassium composition contained the same amount (orslightly lower amounts) of 5-chloro-acesulfame potassium.

The treatment steps did not show a marked reduction in5-chloro-acesulfame potassium content. It is believed that because thechemical structure of chloro-acesulfame potassium is similar to that ofacesulfame potassium, separation of chloro-acesulfame potassium usingstandard purification procedures such as crystallization is ineffective.This analysis demonstrates the importance of reducing/eliminating theproduction of 5-chloro-acesulfame potassium during the steps leading tothe formation of the crude acesulfame composition as described herein.

While the invention has been described in detail, modifications withinthe spirit and scope of the invention will be readily apparent to thoseof skill in the art. In view of the foregoing discussion, relevantknowledge in the art and references discussed above in connection withthe Background and Detailed Description, the disclosures of which areall incorporated herein by reference. In addition, it should beunderstood that aspects of the invention and portions of variousembodiments and various features recited above and/or in the appendedclaims may be combined or interchanged either in whole or in part. Inthe foregoing descriptions of the various embodiments, those embodimentswhich refer to another embodiment may be appropriately combined withother embodiments as will be appreciated by one of skill in the art.Furthermore, those of ordinary skill in the art will appreciate that theforegoing description is by way of example only, and is not intended tolimit the invention.

We claim:
 1. A process for producing a finished acesulfame potassiumcomposition, the process comprising the steps of: (a) contacting asolvent and a cyclizing agent to form a cyclizing agent composition; (b)reacting an acetoacetamide salt with the cyclizing agent in thecyclizing agent composition to form a cyclic sulfur trioxide adduct; and(c) forming from the cyclic sulfur trioxide adduct the finishedacesulfame potassium composition comprising non-chlorinated acesulfamepotassium and less than 35 wppm 5-chloro-acesulfame potassium; whereincontact time from the beginning of step (a) to the beginning of step (b)is less than 60 minutes.
 2. The process of claim 1, wherein the formingcomprises: hydrolyzing the cyclic sulfur trioxide adduct to form anacesulfame-H composition comprising acesulfame-H; neutralizing theacesulfame-H in the acesulfame-H composition to form a crude acesulfamepotassium composition comprising non-chlorinated acesulfame potassiumand less than 35 wppm 5-chloro-acesulfame potassium; and forming thefinished acesulfame potassium composition from the crude acesulfamepotassium composition.
 3. The process of claim 2, wherein the finishedacesulfame potassium composition comprises from 0.001 wppm to 5 wppm5-chloro-acesulfame potassium.
 4. The process of claim 2, wherein thecontact time is less than 15 minutes and the crude acesulfame potassiumcomposition comprises from 0.001 wppm to 5 wppm 5-chloro-acesulfamepotassium and the finished acesulfame potassium composition comprisesfrom 0.001 wppm to 5 wppm 5-chloro-acesulfame potassium.
 5. The processof claim 2, wherein the contact time is less than 5 minutes and thecrude acesulfame potassium composition comprises from 0.001 wppm to 5wppm 5-chloro-acesulfame potassium and the finished acesulfame potassiumcomposition comprises from 0.001 wppm to 2.7 wppm 5-chloro-acesulfamepotassium.
 6. The process of claim 2, wherein the crude acesulfamepotassium composition comprises less than 35 wppm 5-chloro-acesulfamepotassium.
 7. The process of claim 5, wherein the finished acesulfamepotassium composition comprises at least 90% by weight of the5-chloro-acesulfame potassium present in the crude acesulfame potassiumcomposition.
 8. The process of claim 2, wherein the hydrolyzingcomprises adding water to the cyclic sulfur trioxide adduct to form ahydrolysis reaction mixture, and wherein the temperature of thehydrolysis reaction mixture is maintained at a temperature ranging from−35° C. to 0° C.
 9. The process of claim 8, wherein the finishedacesulfame potassium composition comprises from 0.001 wppm to 5 wppmorganic impurities.
 10. The process of claim 1, further comprising:reacting sulfamic acid and an amine to form an amidosulfamic acid salt;and reacting the amidosulfamic acid salt and acetoacetylating agent toform the acetoacetamide salt.
 11. The process of claim 1, wherein thefinished acesulfame potassium composition comprises from 0.001 wppm to2.7 wppm 5-chloro-acesulfame potassium.
 12. The process of claim 1,wherein the finished acesulfame potassium composition comprises from0.001 wppm to 5 wppm organic impurities.
 13. The process of claim 1,wherein the finished acesulfame potassium composition comprises from0.001 wppm to 5 wppm heavy metals.
 14. The process of claim 1, whereinthe cyclizing agent composition comprises less than 1 wt % of compoundsselected from chloromethyl chlorosulfate, methyl-bis-chlorosulfate, andmixtures thereof.
 15. The process of claim 1, wherein the reacting isconducted for a cyclization reaction time, from the start of thereactant feed to the end of the reactant feed, less than 35 minutes. 16.The process of claim 1, wherein the weight ratio of solvent to cyclizingagent in the cyclizing agent composition is at least 1:1.
 17. Theprocess of claim 1, further comprising cooling the cyclizing agentcomposition to a temperature less than 15° C.
 18. The process of claim1, wherein the cyclizing agent comprises sulfur trioxide and the solventcomprises dichloromethane.
 19. A finished acesulfame potassiumcomposition produced from the process of claim
 1. 20. The finishedacesulfame potassium composition of claim 19, comprising:non-chlorinated acesulfame potassium; from 0.001 wppm to 2.7 wppm5-chloro acesulfame potassium; and from 0.001 wppm to 5 wppm heavymetals.
 21. A process for producing a finished acesulfame potassiumcomposition, the process comprising the steps of: reacting sulfamic acidand triethylamine to form an amidosulfamic acid salt; reacting theamidosulfamic acid salt and diketene to form the acetoacetamide salt;contacting dichloromethane and a sulfur trioxide to form a cyclizingagent composition; reacting the acetoacetamide salt with the sulfurtrioxide in the cyclizing agent composition to form a cyclic sulfurtrioxide adduct; hydrolyzing the cyclic sulfur trioxide adduct to forman acesulfame-H composition; and neutralizing the acesulfame-H in theacesulfame-H composition to form crude acesulfame potassium compositioncomprising non-chlorinated acesulfame potassium and less than 35 wppm5-chloro-acesulfame potassium; and forming from crude acesulfamepotassium composition the finished acesulfame potassium compositioncomprising non-chlorinated acesulfame potassium and less than 10 wppm5-chloro-acesulfame potassium, wherein contact time from the beginningof step (a) to the beginning of step (b) is less than 10 minutes. 22.The process of claim 21, further comprising cooling the cyclizing agentcomposition to a temperature less than 15° C.
 23. An acesulfamepotassium composition comprising non-chlorinated acesulfame potassiumand less than 35 wppm 5-chloro-acesulfame potassium.
 24. The acesulfamepotassium composition of claim 23, further comprising less than 37 wppmacetoacetamide-N-sulfonic acid.
 25. The acesulfame potassium compositionof claim 23, further comprising 0.001 wppm to 5 wppm organic impuritiesand/or 0.001 wppm to 5 wppm of at least one heavy metal.
 26. Theacesulfame potassium composition of claim 25, wherein the at least oneheavy metal is selected from the group consisting of mercury, lead andmixtures thereof.
 27. The acesulfame potassium composition of claim 26,wherein the mercury is present in an amount of 1 wppb to 20 wppm. 28.The acesulfame potassium composition of claim 26, wherein the lead ispresent in an amount of 1 wppb to 25 wppm.